Advancing Cognitive Health: The Role of NMN, Metformin, and Rapamycin in Combating Vascular Cognitive Impairment

When discussing dementia, Alzheimer's disease often steals the spotlight. However, VCI, the second most common cause of dementia, quietly impacts millions. VCI emerges from reduced blood flow to the brain, often due to cardiac conditions or disorders such as high cholesterol, leading to cognitive degradation. Until now, VCI had no promising therapeutic avenues to delay or prevent its progression.

The Impact of NMN, Metformin, and Rapamycin

In a study published in Frontiers in Neurology, Jin and his team at the University of North Texas presented exciting findings that pretreatment with nicotinamide mononucleotide (NMN), metformin, or rapamycin might potentially curtail cognitive decline linked to VCI. They found that these compounds not only diminish brain lesions caused by VCI but also forestall the degradation of myelin, a fatty tissue essential for rapid neuron firing.

The Experiment: Protecting Cognitive Function through Proactive Measures

To assess the potential of NMN, metformin, and rapamycin, the team administered these compounds to rats for 14 days before inducing conditions mimicking VCI. Using the Morris water maze, an assessment tool for learning and memory, they found that rats pretreated with any of these compounds displayed enhanced memory performance, thus demonstrating their potential to safeguard cognition in the face of reduced blood flow to the brain, as seen in VCI.

The Underlying Mechanisms: A Deep Dive into Cellular Dynamics

Digging deeper into the cellular mechanics, Jin's team discovered that these compounds significantly reduced the number of brain lesions, implying the preservation of healthy brain tissue. They further found that these compounds prevented the degradation of myelin, a critical element for quick brain response and cognition.

The Common Thread: NMN, Metformin, and Rapamycin in Myelin Preservation

It is crucial to understand how NMN, metformin, and rapamycin impact brain tissue under VCI-like conditions. Current research suggests that they all influence similar pathways to prevent myelin degradation. For instance, rapamycin inhibits the protein mTOR, which puts microglia cells in a degradation state. Metformin stimulates AMP-activated protein kinase (AMPK) proteins, which similarly suppress mTOR activity. NMN activates Sirtuin1 proteins, which subsequently trigger AMPK to inhibit mTOR, thus preventing microglia activation.

The Cost-Benefit Analysis: Which Compound Reigns Supreme?

As all three compounds demonstrate similar benefits, it becomes imperative to consider their cost-effectiveness. Metformin, costing approximately $13.72 per month, and rapamycin, priced around $100 per month, both inhibit mTOR. However, metformin also regulates glucose metabolism, which is beneficial for type 2 diabetes patients. NMN, costing roughly $50 per month, offers a more extensive range of benefits. It not only stimulates sirtuin proteins to combat cell oxidative stress but also promotes mitochondrial function and suppresses mTOR by activating AMPK.

Wrapping Up: A New Ray of Hope for VCI Patients

Despite being the second leading cause of dementia, VCI has been a silent and unaddressed concern. This groundbreaking study by Jin and his team highlights the potential of NMN, metformin, and rapamycin as viable therapeutic options to tackle cognitive decline related to VCI, offering renewed hope to those affected by this condition. As we move forward, it will be exciting to see how these findings translate into real-world applications and transform the landscape of VCI treatment.

References

Yu M, Zheng X, Cheng F, Shao B, Zhuge Q, Jin K. Metformin, Rapamycin, or Nicotinamide Mononucleotide Pretreatment Attenuate Cognitive Impairment After Cerebral Hypoperfusion by Inhibiting Microglial Phagocytosis. Front Neurol. 2022 Jun 13;13:903565. doi: 10.3389/fneur.2022.903565. PMID: 35769369; PMCID: PMC9234123.